The present invention relates to compounds having a polyene chain structure, and processes for preparing the same. More specifically, it relates to intermediate compounds, which can be effectively used in the synthesis of xcex2-carotene, processes for preparing the same, processes for preparing xcex2-carotene by using the intermediate compounds, and xe2x80x9cretinyl sulfide,xe2x80x9d named by the present inventors, and a process for preparing the same.
Carotenoid compounds have a polyene chain structure, and specific examples of such include xcex2-carotene, lycopene, astaxanthin and the like. xcex2-carotene is known as pro-vitamin A, which decomposes to vitamin A according to the needs of a living body.
Carotenoid compounds are generally used as natural pigments for foodstuffs, and are apt to selectively react with carcinogens such as singlet oxygen radical and the like, and as such, they are expected to have use as a prophylactic agent for cancers. In light of this expectation, there is an increasing need to develope a process that can effectively and efficiently synthesize the polyene chain structure.
xcex2-carotene has been manufactured by Hoffmann-La Roche since 1954, and by BASF since 1972 [Paust, J., Pure Appl. Chem., 63:45-58 (1991)].
According to the Roche process, two C19 molecular units are connected by using bis(magnesium halide) acetylide, and the resulting product is subjected to partial hydrogenation of the triple bond and dehydration in the presence of acid catalyst, to provide xcex2-carotene, as shown in Scheme 1 below: 
As can be seen from Scheme 1, however, the synthesis of the C19 compound from the C14 compound is not a convergent process, and requires two consecutive enol ether condensations, thereby providing the process with a low effectiveness.
With regard to the BASF process, xcex2-carotene is synthesized via a Wittig reaction of C15 phosphonium salt and C10 dialdehyde, as is shown in Scheme 2 below. According to this process, a double bond can be effectively formed by the Wittig reaction, but the process has a further problem in that phosphine oxide (Ph3Pxe2x95x90O), produced as a by-product, cannot be easily separated or removed. 
The present invention provides intermediate compounds useful for the efficient synthesis of the polyene chain structure, taking full advantage of its symmetry and which solve the problem of by-products such as phosphine oxide by the employment of the Julia-type sulfone olefination strategy; processes for preparing the same; and processes for preparing xcex2-carotene using the same.
The present invention also provides a novel compound having a polyene chain structure which is synthesized via the aforementioned intermediate compound, and a process for preparing the same.
The present invention further provides an improved process for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dial, a compound used in the BASF process for preparing xcex2-carotene, which requires fewer synthetic steps than the conventional process.
Accordingly, one embodiment of the invention is a diallylic sulfide, represented by Chemical Formula 1: 
wherein, R1 and R2 are independently chosen from the group consisting of xe2x80x94CHO, xe2x80x94CH2Cl, xe2x80x94CH2Br, xe2x80x94CH2I, xe2x80x94CH2OH, xe2x80x94CH2OSO2CF3, xe2x80x94CH2OSO2Ph, xe2x80x94CH2OSO2C6H4CH3 and xe2x80x94CH2OSO2CH3. Preferably, R1 and R2 are both xe2x80x94CHO or xe2x80x94CH2Cl.
Another embodiment of the present invention is a process for preparing a diallylic sulfide represented by Chemical Formula 1, which comprises the steps of:
(a) oxidizing isoprene to give isoprene monoxide;
(b) reacting the isoprene monoxide with cupric halide (CuX2)/lithium halide (LiX) to provide an allylic halide (A); and
(c) reacting the allylic halide (A) with sodium sulfide (Na2S) to produce a compound represented by Chemical Formula 1.
The process may be represented by: 
wherein R1 and R2 are independently chosen from the group consisting of xe2x80x94CHO, xe2x80x94CH2Cl, xe2x80x94CH2Br, xe2x80x94CH2I, xe2x80x94CH2OH, xe2x80x94CH2OSO2CF3, xe2x80x94CH2OSO2Ph, xe2x80x94CH2OSO2C6H4CH3 and xe2x80x94CH2OSO2CH3, and X is chosen from Cl, Br and I.
For the diallylic sulfides represented by Chemical Formula 1, wherein R1 and R2 are xe2x80x94CH2Cl, xe2x80x94CH2Br or xe2x80x94CH2I, the synthesis comprises the further step of reducing and halogenating the resultant product from step (c).
Step (c) is preferably performed via the sequence of: (1) adding a catalytic amount of acid to the allylic halide (A) in alcoholic solvent to form an acetal in situ; (2) reacting said acetal with sodium sulfide for a predetermined period; and (3) evaporating the solvent and hydrolyzing the residue.
Another embodiment of the present invention provides a process for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dial represented by Chemical Formula 2, which comprises the steps of:
(a) protecting the aldehyde group of allylic halide (A) to provide the corresponding acetal compound (G);
(b) reacting the acetal compound (G) with Na2S to provide di(3-formyl-3-methyl-2-propenyl)sulfide, dialkyl diacetal (H);
(c) selectively oxidizing the di(3-formyl-3-methyl-2-propenyl) sulfide, dialkyl diacetal (H) to provide the corresponding allylic sulfone compound (I);
(d) applying a Ramberg-Bxc3xa4cklund reaction to the allylic sulfone compound (I) to provide the corresponding triene compound (J); and
(e) hydrolyzing the triene compound (J) to provide 2,7-dimethyl-2,4,6-octatriene-1,8-dial, represented by Chemical Formula 2. 
Here, X represents a halogen atom and R3 and R4 independently represent hydrogen or a methyl group.
In this embodiment, the selective oxidation reaction of step (c) is preferably performed by adding a mixture of urea-hydrogen peroxide (here-in-after, referred to as xe2x80x9cUHPxe2x80x9d) and phthalic anhydride dropwise to a solution containing di(3-formyl-3-methyl-2-propenyl)sulfide, dialkyl diacetal at low temperature.
Yet another embodiment of the invention provides a process for preparing xcex2-carotene represented by Chemical Formula 3, which comprises the steps of:
(a) deprotonating the sulfone compound (B), and reacting not more than xc2xd equivalent (based on the sulfone compound) of allylic sulfide (C) represented by Chemical Formula 1 (R1, R2=CH2X, X=halogen atom) thereto, to provide sulfide compound (D);
(b) selectively oxidizing the sulfide compound (D) to prepare the sulfone compound (E);
(c) subjecting the sulfone compound (E) to a Ramberg-Bxc3xa4cklund reaction to prepare 11,20-di(benzenesulfonyl)-11,12,19,20-tetrahydro-xcex2-carotene (F); and
(d) reacting 11,20-di(benzenesulfonyl)-11,12,19,20-tetrahydro-xcex2-carotene (F) with a base to provide -xcex2-carotene, represented by Chemical Formula 3. 
In this embodiment, when X is Cl, step (a) is preferably performed by adding a stoichiometric amount of sodium iodide (NaI) in terms of reactivity. The selective oxidation of step (b) is preferably carried out by adding a mixture of UHP and phthalic anhydride dropwise to a solution containing the sulfide compound (D) at low temperature.
The base used in step (d) is not specifically restricted. Appropriate bases include, but are not limited to, for example, NaNH2/NH3, metal alkoxides such as CH3OK/CH3OH, CH3CH2OK/CH3CH2OH and CH3CH2ONa/CH3CH2OH, and t-BuOK/t-BuOH. Among these example, metal alkoxides are more preferable.
Yet another embodiment of the present invention provides a novel compound, retinyl sulfide, represented by Chemical Formula 4: 
Still another embodiment of the present invention provides a process for preparing retinyl sulfide represented by the Chemical Formula 4, which comprises a Wittig reaction of diallylic sulfide (C-1) represented by Chemical Formula 1 (R1 and R2 are each xe2x80x94CHO) and the Wittig salt (K). 
The diallylic sulfide represented by Chemical Formula 1, which is used as a basic material in the synthesis of compounds having polyene chain structure, may be synthesized according to the following procedure, illustrated in Scheme 3, below.
First, isoprene is oxidized to obtain isoprene monoxide. The oxidation may be carried out under the condition of using an oxidant such as m-chloroperoxybenzoic acid (MCPBA), or the condition of forming a corresponding halohydrin, which is then reacted with a base [J. Am. Chem. Soc, 72:4608 (1950)], or the like. Among these, the latter process is more preferable, when considering the regio-selectivity on two double bonds of isoprene.
Then, said isoprene monoxide is subjected to ring opening reaction by reacting with cupric halide (CuX2xc2x72H2O)/lithium halide (LiX), to obtain allylic halide (A). For the ring opening reaction, the reaction condition disclosed in literature [J. Org. Chem., 41:1648 (1976)] is referred, and the reaction condition of cupric chloride (CuCl2xc2x72H2O)/lithium chloride (LiCl) is preferably employed.
Then, from the allylic halide (A), diallylic sulfide represented by Chemical Formula 1 is obtained. 
In this process, when R1 and R2 are each aldehyde groups, allylic halide (A) is allylated to obtain diallylic sulfide (Chemical Formula 1) which has aldehyde functional groups at both ends. The allylation is preferably carried out by adding a catalytic amount of acid such as p-toluenesulfonic acid (p-TsOH) in alcoholic solvent to form an acetal, which is then reacted with sodium sulfide and hydrolyzed. In such a reaction condition, allylation can be proceeded without side reactions. The acid such as p-TsOH serves as a catalyst that promotes the formation of acetal.
As seen in Scheme 4, below, when R1 and R2 are each xe2x80x94CH2X (wherein, X is a halogen atom), the allylic sulfide is first reduced to give the corresponding diol compound (C-1), which is then halogenated to obtain diallylic sulfide (C) in which halogen atoms have been introduced at both ends. The halogenation of diol compounds may be carried out under various reaction conditions. For example, halogenation is performed by using a reaction condition of CH3SO2Cl/LiCl, HCl, HBr, PPh3/CCl4, or the like. 
As previously discussed, 2,7-dimethyl-2,4,6-octatriene-1,8-dial represented by Chemical Formula 2 is an important compound used in the synthesis of xcex2-carotene of Chemical Formula 3, by reacting with Wittig salt (K) according to the BASF process. Here-in-after, the process for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dial of Chemical Formula 2 is described with reference to Scheme 5 below.
First, the aldehyde group of the allylic halide (A) must be protected. The protection of aldehyde group is performed by converting the compound to the corresponding cyclic acetal compound (G) by using glycol compounds such as neopentyl glycol, propylene glycol, ethylene glycoi, or the like.
The cyclic acetal compound (G) is then reacted with Na2S to obtain the corresponding allylic sulfide, dialkyl diacetal (H). The compound (H) may be used as a basic material for the synthesis of compounds having polyene chain structure.
The sulfur of the compound (H) is then selectively oxidized to obtain the corresponding allylic sulfone compound (I). The selective oxidation is performed under a condition of slowly adding an oxidant to the allylic sulfide compound (H) at low temperature. As the oxidant, peroxyphthalic acid, which is the resulting product of reaction of UHP and phthalic anhydride, is preferably used.
Through a Ramberg-Bxc3xa4cklund reaction, the corresponding triene compound (J) is obtained from the allylic sulfone compound (I). Deprotection by hydrolysis of acetal groups of the triene compound (J) gives 2,7-dimethyl-2,4,6-octatriene-1,8-dial represented by Chemical Formula 2. 
The process for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dial described herein requires fewer steps than the conventional process, making the process simpler in terms of manufacturing.
Referring now to Scheme 6, the process for preparing xcex2-carotene of Chemical Formula 3, according to the present invention, is described. The process is characterized in that a Ramberg-Bxc3xa4cklund reaction is performed on diallylic sulfone which was obtained by the oxidation of diallylic sulfide, as previously described herein.
According to the process, allylic sulfide (C) and 2 equivalents or more of sulfone compound (B) based on the amount of the allylic sulfide are first coupled according to the Julia process (Bull. Soc. Chim. Fr., 1973). As a result of the coupling, the allylic sulfide (D) is obtained, which contains all the carbons required for the synthesis of xcex2-carotene. The coupling reaction of allylic sulfide (C) with sulfone compound (B) may be carried out under various reaction conditions. If X is Cl, it is preferable to quantitatively add sodium iodide (NaI). Under such a reaction condition, the halogen atoms at both end of allylic sulfide (C) are substituted by iodine, and then allylation of the sulfone compound actively occurs.
Then, the sulfur atom only of allylic sulfide (D) is selectively oxidized to obtain the corresponding sulfone compound (E). The selective oxidation is preferably carried out under the reaction condition of adding an oxidant to the allylic sulfide compound at low temperature. Under such a reaction condition, the double bond of allylic sulfide (D) is not oxidized, but only the sulfur is selectively oxidized.
Subsequently, SO2 of the central part of the structure of sulfone compound (E) is removed by forming a double bond, to give compound (F). Preferably, the reaction is carried out by applying a Ramberg-Bxc3xa4cklund reaction to sulfone compound (E).
Compound (F) is then heated in the presence of alcoholic solvent and alkoxide base such as sodium alkoxide to remove two benzenesulfonyl groups, thereby obtaining xcex2-carotene of Chemical Formula 3. 
In accordance with the present invention, retinyl sulfide of Chemical Formula 4 may be obtained by a Wittig reaction wherein the allylic sulfide having aldehyde groups at both ends is reacted with Wittig salt (K), as illustrated in Scheme 7 below. 
As retinyl sulfide of Chemical Formula 4 has a structure wherein the units of vitamin A are linked by a sulfur atom, the compound is expected to exhibit the activity of vitamin A.